Case Report: Intellectual disability and borderline intellectual functioning in two sisters with a 12p11.22 loss.

Multiple genome sequencing studies have identified genetic abnormalities as major causes of severe intellectual disability (ID). However, many children affected by mild ID and borderline intellectual functioning (BIF) lack a genetic diagnosis because known causative ID genetic mutations have not been identified or the role of genetic variants in mild cases is less understood. Genetic variant testing in mild cases is necessary to provide information on prognosis and risk of occurrence. In this study, we report two sibling patients who were 5 years 9 months old and 3 years 3 months old and presented to the hospital due to developmental delay. Clinical assessment and chromosomal microarray analysis were performed. The patients were diagnosed with mild intellectual disability (ID) and borderline intellectual functioning (BIF). Genetic analysis identified a loss of 12p11.22, including the OVCH1-AS1, OVCH1, and TMTC1 genes, which was the only variant that occurred in both sisters. Identical variants were found in their father with probable BIF. Neither patient presented any brain structural abnormalities or dysmorphism, and no exogenous factors or parenting problems were reported. Thus, loss of 12p11.22 may be associated with our patients' cognitive impairment. The OVCH1, OVCH1-AS1 and TMTC1 variants identified in this study are the most likely disease-causing genes in the sisters. Our findings may expand as yet limited knowledge on mild ID and BIF causative variants, which would further support the diagnosis even if the severity is mild.

Interaction between 12p chromosomal abnormalities and Lnc-HOTAIR mediated pathway in acute myeloid leukemia.

OBJECTIVES: To investigate the correlation of homeobox (HOX) transcript antisense RNA expression with clinicopathological features and the clinical prognosis of the patients with chromosome 12p abnormalities associated acute myeloid leukemia (AML). We also investigate the association of 12p chromosomal on the expression of HOTAIR, miRNA-193a, and c-kit gene as targeting genes for HOTAIR in AML. METHODS: AML patients with 12p chromosomal abnormalities were recruited and compared to AML with other chromosomal abnormalities rather than 12p. The long noncoding RNA (lncRNA) "HOTAIR," miR-193a, and c-Kit genes expression were measured in bone marrow samples using Syber green based real-time polymerase chain reaction. RESULTS: We found a significant difference for the expression levels of HOTAIR, c-kit, and miR-193a between 12p abnormalities associated AML and those without. The survival analysis revealed that patient's with low expression levels of HOTAIR and c-kit had significantly better survival and leukemia free survival. In contrast, miR-193a was associated with better overall survival but not leukemia free survival. CONCLUSION: 12p abnormalities associated AML were associated with worse prognosis. Our results proved that HOTAIR, miR-193a, and c-kit genes are independent prognostic predictors in 12p chromosomal associated AML; therefore it may represent a novel therapeutic application in AML in the future.

Chromosome 12p Deletion Spanning the GRIN2B Gene Presenting With a Neurodevelopmental Phenotype: A Case Report and Review of Literature.

The GRIN2B (glutamate receptor, ionotropic, N-methyl-d-aspartate 2B) gene, located in the short arm of chromosome 12, encoding the NR2B subunit of the N-methyl-D-aspartate receptor, has recently been recognized to play an important role in corticogenesis and brain plasticity. Deletions in the short arm of chromosome 12 are rare. Hemizygous loss of function of the GRIN2B gene results in developmental delay, whereas gain of function leads to epilepsy, and infantile spasms in particular. In addition, GRIN2B variants have been associated with autism spectrum disorder and schizophrenia. Here the authors report a child with global developmental delay, autistic behavioural features, central hypotonia, dysmorphic features and isolated congenital anomalies of the fingers and toes, and a de novo heterozygous deletion in chromosome locus 12p13.2-p13.1, involving loss of several genes, including GRIN2B. This report and our review of the literature help clarify the distinct phenotypes associated with loss or gain of GRIN2B function.

Genomic deletion of chromosome 12p is an independent prognostic marker in prostate cancer.

Deletion of 12p is a recurrent alteration in prostate cancer, but the prevalence and clinical consequences of this alteration have not been studied in detail. Dual labeling fluorescence in situ hybridization using probes for 12p13 (CDKN1B; p27) and centromere 12 as a reference was used to successfully analyze more than 3700 prostate cancers with clinical follow-up data assembled in a tissue microarray format. CDKN1B was selected as a probe because it is located in the center of the deletion, which spans > 10 Mb and includes > 50 genes in 80% of cancers with 12p deletion. Deletion of 12p was found in 13.7% of cancers and included 13.5% heterozygous and 0.2% homozygous deletions. 12p deletion were linked to advanced tumor stage (p < 0.0001), high Gleason grade (p < 0.0001), rapid tumor cell proliferation (p < 0.0001), lymph node metastasis (p = 0.0004), and biochemical recurrence (p = 0.0027). Multivariate analysis including pT stage (p < 0.0001), Gleason grade (p < 0.0001), pN status (p = 0.0001), preoperative PSA levels (p = 0.0001), and resection margin status (p = 0.0001) revealed an independent prognostic value of 12p deletion (p = 0.0014). Deletion of 12p was unrelated to the ERG fusion status. Deletion of 12p was only marginally linked to reduced p27 expression, which by itself was unrelated to clinical outcome. This argues against p27 as the key target gene of 12p deletions. In summary, the results of our study demonstrate that 12p deletion is frequent in prostate cancer and provides independent prognostic information. 12p deletion analysis alone, or in combination with other prognostic parameters may thus have clinical utility.